We demonstrate that a new free energy functional in the integral equation theory of molecular liquids gives accurate calculations of hydration thermodynamics for druglike molecules. The functional provides an improved description of excluded volume effects by incorporating two free coefficients. When the values of these coefficients are obtained from experimental data for simple organic molecules, the hydration free energies of an external test set of druglike molecules can be calculated with an accuracy of about 1 kcal/mol. The 3D RISM/UC method proposed here is easily implemented using existing computational software and allows in silico screening of the solvation thermodynamics of potential pharmaceutical molecules at significantly lower computational expense than explicit solvent simulations.